The Plasmodium berghei merozoite protein PbGAC is critically involved in erythrocyte binding during invasion.

BACKGROUND

The invasion of Plasmodium merozoites into host erythrocytes is initiated through specific ligand-receptor interactions. This interaction results in subsequent invasion events, facilitated by the formation of a moving junction via AMA-1 and associated molecular complexes. Previous studies have implicated erythrocyte surface glycosaminoglycans, particularly heparan sulfate proteoglycans, as critical receptor components in this invasion process.

METHODS

The binding affinity of the PbGAC protein to heparin and erythrocytes was assessed through western blotting, immunofluorescence, flow cytometry techniques, and heparinase II treatment. Mice were immunized with the recombinant PbGAC-His to generate specific polyclonal antibodies for subcellular localization, passive immunization, and immunoprecipitation. Global mass spectrometric analyses were conducted to identify its interacting proteins.

RESULTS

We elucidated the molecular function of PbGAC (encoded by PbANKA_1137800), a previously uncharacterized Plasmodium berghei ANKA protein, in association with merozoite attachment and invasion via the heparan sulfate-dependent pathway. The PbGAC protein, predominantly located at the extreme apical region of the P. berghei merozoite, binds to heparin and the erythrocyte surface during merozoite invasion. Global mass spectrometric analysis reveals that PbGAC interacts with several secreted proteins that are critically involved in erythrocyte invasion. In addition, mice either immunized with the PbGAC protein or passively immunized with sera derived from vaccinated mice demonstrated enhanced immunity against lethal challenges.

CONCLUSIONS

Our findings pinpointed that PbGAC is predominantly expressed at the extreme apical region of the P. berghei merozoite and engaged in binding to the heparin-like receptors on the erythrocyte surface during merozoite invasion.